Rothmund reported a disease characterized by poikiloderma and juvenile cataract (Rothmund, A. (1868) Uber cataracten in verbindung mit einer eigenthumlichen hautdegeneration. Arch. Klin. Exp. Ophthal., 4, 159-182.). Thomson reported a disease characterized by poikiloderma and genetic osteogenesis abnormalities (Thomson, M. S. (1936) Poikiloderma congenitale. Br. J. Dermatol., 48, 221-234). These diseases were later found to be part of the same syndrome, designated Rothmund-Thomson syndrome. Rothmund-Thomson syndrome (hereinafter abbreviated “RTS”) is an autosomal recessive genetic disease characterized by growth disorder, poikiloderma, hair loss, cataracts, osteogenesis abnormalities and a high incidence of osteosarcomas (Ichikawa, K., Noda, T. and Furuichi, Y. (2002) Preparation of the gene targeted knockout mice for human premature aging diseases, Werner syndrome, and Rothmund-Thomson syndrome caused by the mutation of DNA helicases. Nippon Yakurigaku Zasshi., 119, 219-226., Vennos, E. M. and James, W. D. (1995) Rothmund-Thomson syndrome. Dermatol. Clin., 13, 143-150., Vennos, E. M., Collins, M. and James, W. D. (1992) Rothmund-Thomson syndrome: review of the world literature. J. Am. Acad. Dermatol., 27, 750-762).
These characteristics also suggest that RTS is a premature aging syndrome. Werner's syndrome which is caused by mutation in WRN gene and Bloom syndrome which is caused by mutation in BLM gene, have been known as typical examples of premature aging syndrome (Mohaghegh, P. and Hickson, I. D. (2001) DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders. Hum. Mol. Genet., 10, 741-746).
The genes belong to RecQ helicase gene family. For RECQL4 gene which belongs to the RecQ helicase gene family, mutations of the RECQL4 gene is identified in many RTS patients. The mutations were frequently identified in the helicase domain of RECQL4 gene (FIG. 1. Arrows). In order to confirm whether RTS is caused by the mutations in the helicase domain of RECQL4 gene to prepare a mouse model for RTS patient, preparation of a RECQL4 gene-disrupted mouse was attempted. However, the mouse wherein exons 5 to 8 in the twenty two exons of RECQL4 gene are knockouted was died between embryonic day 3.5 to 6.5 (Ichikawa, K., Noda, T. and Furuichi, Y. (2002) Preparation of the gene targeted knockout mice for human premature aging diseases, Werner syndrome, and Rothmund-Thomson syndrome caused by the mutation of DNA helicases. Nippon Yakurigaku Zasshi., 119, 219-226). Therefore, the preparation of the mouse model for RTS had not been unsuccessful.